Gene/Protein Disease Symptom Drug Enzyme Compound
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 21,692 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In a Review-Hypothesis, Mitchell [(1987) FEBS Lett. 222,235-245] has recently suggested possible molecular mechanisms for proton translocation by cytochrome oxidase. In describing these mechanisms, he extended his own concept of a redox loop in a manner expected to lead to confusion. He also stated that the term redox-linked proton pump implies an indirect coupling between electron transfer and proton translocation, and that this type of coupling is very difficult to test experimentally. Here it is argued that the original meaning of a redox loop should be maintained, and proper definitions of the terms redox-linked proton pump and direct or indirect coupling are formulated. In addition, it is reasoned that both types of coupling are amenable to experimental tests.
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PMID:Redox loops and proton pumps. 283 27

Omeprazole has been marketed in France since 1989, for the healing of peptic ulcers, erosive reflux esophagitis and the Zollinger Ellison syndrome. It is a proton pump inhibitor which inhibits the acid secretion in the stomach. In the majority of the clinical trials, omeprazole has been found to be well tolerated: headache, dizziness, skin rash, constipation have just been noted. Since September 1989, 143 adverse reactions have been reported to pharmacovigilance centres and Astra France: 37 neurological and psychiatric side effects, especially confusion in patients with hepatic diseases and/or advanced age; 35 cutaneous reactions, generally rash and urticaria; 22 hematological effects: leucopenia and agranulocytosis have been reported but the relation with omeprazole is very uncertain; 10 gastrointestinal effects, generally diarrhoea, nausea, vomiting and abdominal pain; 8 hepatic disorders, especially moderate elevation of aminotransferases. This study confirms the safety of this drug, during short treatment; the frequency of notified adverse effects is about 1/12 200 treatments of 4 weeks. The ministry of health, has decided, in november 1991, to inform the prescribers of this potential toxicity of omeprazole, particularly, of the risk of confusion, hepatotoxicity and leucopenia.
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PMID:[Evaluation of unexpected and toxic effects of omeprazole (Mopral) reported to the regional centers of pharmacovigilance during the first 22 postmarketing months]. 814 27

Since the discovery of Helicobacter pylori, a considerable amount of progress has been made in our understanding of H. pylori-related conditions. However, considerable confusion exists in relation to the optimal application of these findings to clinical practice, particularly at a primary care setting. In the USA the National Institutes of Health published guidelines outlining the role of H. pylori in peptic ulcer disease in 1994. Since then at least eight European countries have issued guidelines. The differences that exist between these documents reflect the rapid evolution of opinion on how the diagnosis and treatment of H. pylori should influence the traditional management of conditions presenting with dyspepsia. It is clear that little controversy surrounds the approach to duodenal and gastric ulceration. Patients with gastric mucosa-associated lymphoid tissue lymphoma need careful follow-up. The greatest level of disagreement exists in relation to the management of non-ulcer dyspepsia and dyspepsia in the community. These areas, in addition to the role of H. pylori eradication when non-steroidal antiinflammatory drugs or long-term acid suppressor are considered, need further evaluation. Most countries now recommend proton pump-based triple therapy regimes as first-line treatment for the eradication of H. pylori.
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PMID:Consensus or confusion: a review of existing national guidelines on Helicobacter pylori-related disease. 918 89

There is considerable confusion over the management of Helicobacter pylori infection, particularly among primary care physicians, and numerous European countries lack national guidelines in this rapidly growing area of medicine. The European Helicobacter Pylori Study Group therefore organised a meeting in Maastricht of H pylori experts, primary care physicians and representatives of National Societies of Gastroenterology from Europe to establish consensus guidelines on the management of H pylori at the primary care and specialist levels, and to consider general health care issues associated with the infection. As in previous guidelines, eradication therapy was recommended in all H pylori positive patients with peptic ulcer disease. Additionally, at the primary care level in dyspeptic patients < 45 years old and with no alarm symptoms, diagnosis is recommended by non-invasive means (13C urea breath test, serology) and if H pylori positive the patient should be treated. Moreover, at the specialist level the indications for eradication of H pylori were also broadened to include H pylori positive patients with functional dyspepsia in whom no other possible causes of symptoms are identified by the specialist (after a full investigation including endoscopy, ultrasound and other necessary investigations), patients with low grade gastric mucosa associated lymphoid tissue (MALT) lymphoma (managed in specialised centres) and those with gastritis with severe macro- or microscopic abnormalities. There was consensus that treatment regimens should be simple, well tolerated and achieve an eradication rate of over 80% on an intention to treat basis. It was strongly recommended, therefore, that eradication treatment should be with proton pump inhibitor based triple therapy for seven days, using a proton pump inhibitor and two of the following: clarithromycin, a nitroimidazole (metronidazole or tinidazole) and amoxycillin.
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PMID:Current European concepts in the management of Helicobacter pylori infection. The Maastricht Consensus Report. European Helicobacter Pylori Study Group. 961 32

Laparoscopic fundoplication controls heartburn and regurgitation, but the effects on the respiratory symptoms of gastroesophageal reflux disease (GERD) are unclear. Confusion stems from difficulty preoperatively in determining whether cough or wheezing is actually caused by reflux when reflux is found on pH monitoring. To date, there is no proven way to pinpoint a cause-and-effect relationship. The goals of this study were to assess the following: (1) the value of pH monitoring in establishing a correlation between respiratory symptoms and reflux; (2) the predictive value of pH monitoring on the results of surgical treatment; and (3) the outcome of laparoscopic fundoplication on GERD-induced respiratory symptoms. Between October 1992 and October 1998, a total of 340 patients underwent laparoscopic fundoplication for GERD. From the clinical findings alone, respiratory symptoms were thought possibly to be caused by GERD in 39 patients (11%). These 39 patients had been symptomatic for an average of 134 months. They were all taking H2-blocking agents (21%) or proton pump inhibitors (79%). Seven patients (18%) were also being treated with bronchodilators, alone (3 patients) or in combination with prednisone (4 patients). Median length of postoperative follow-up was 28 months. In 23 patients (59%) a temporal correlation was found during 24-hour pH monitoring between respiratory symptoms and episodes of reflux. Postoperatively heartburn resolved in 91% of patients, regurgitation in 90% of patients, wheezing in 64% of patients, and cough in 74% of patients. Cough resolved in 19 (83%) of 23 patients in whom a correlation between cough and reflux was found during pH monitoring, but in only 8 (57%) of 14 of patients when this correlation was absent. Cough persisted postoperatively in the two patients who did not cough during the study. These data show that pH monitoring helped to establish a correlation between respiratory symptoms and reflux, and it helped to identify the patients most likely to benefit from antireflux surgery. Following laparoscopic surgery, respiratory symptoms resolved in 83% of patients when a temporal correlation between cough and reflux was found on pH monitoring; heartburn and regurgitation resolved in 90%.
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PMID:Effect of laparoscopic fundoplication on gastroesophageal reflux disease-induced respiratory symptoms. 1067 37

Helicobacter pylori infection and the use of non-steroidal anti-inflammatory drugs (NSAIDs) can each result in gastroduodenal ulcers and ulcer complications. Recent studies have suggested that there is an interaction between the two causes such that elimination of H. pylori before NSAID treatment decreases the occurrence of ulcers. This led to the conclusion of the Maastricht 2000 meeting that H. pylori eradication should be considered before embarking on long-term NSAID therapy. One of the main sources of confusion is related to the fact that prospective endoscopic studies testing various drugs for prevention of NSAID ulcers among chronic NSAID users are probably not directly applicable to problems of clinical ulcers and of ulcer complications. It has become clear that, to be interpretable clinically, such studies must provide separate analyses based on H. pylori status, history of ulcer, or an ulcer complication. Overall, the data strongly support the notion that eradication therapy is beneficial for primary prophylaxis. In contrast, one would expect little benefit when NSAIDs caused the clinical ulcer (secondary prevention) and, at best, H. pylori eradication has a modest effect on the prevention of recurrent ulcer bleeding in NSAID users who have suffered ulcer complications. The data support the notion that H. pylori eradication therapy should be given to all H. pylori -infected patients with peptic ulcers irrespective of whether or not they have used NSAIDs. Proton pump inhibitors are superior to placebo for the prevention of ulcer recurrence but are inferior to full-dose misoprostol for the prevention of ulcers among those with NSAID ulcers and no H. pylori infection. Selective COX-2 inhibitors appear to reduce markedly, but not eliminate, ulcer complications among chronic NSAID users.
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PMID:Helicobacter pylori infection and the use of NSAIDs. 1156 40

The availability of clinic-based diagnostic tests means that screening for and the eradication of Helicobacter pylori can be done by primary care physicians. However, confusion still exists regarding indication and treatment regimens. It is universally accepted that patients with Helicobacter pylori infection and peptic ulcer disease require eradication therapy. But the benefits of Helicobacter pylori eradication in gastro-oesophageal reflux disease, non-steroidal anti-inflammatory drug-related peptic ulceration, and non-ulcer dyspepsia remain unclear. There is no evidence that the elimination of Helicobacter pylori is beneficial for asymptomatic patients or in preventing gastric cancer. One-week triple therapy with a proton pump inhibitor or ranitidine bismuth citrate in combination with clarithromycin/metronidazole and amoxycillin is the recommended first-line treatment for Helicobacter pylori infection. Problems with patient compliance and the development of antibiotic resistance are the two most important factors to consider when choosing the treatment regimen. The optimal retreatment therapy for treatment failure is still unknown, and quadruple therapy is best reserved for these cases.
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PMID:Treatment of Helicobacter pylori infection. 1182 83

Critics have questioned the foundational principles of pharmacological sciences and modern drug therapy; they also claim that drug therapy is often too expensive or of uncertain value. Contemporaneously, alternative medicine has bloomed. Yet the US government began to pay for drug therapy under Medicare in 2006, an explicit recognition of the value of modern drug therapy. To clarify this confusion, we review the philosophical and scientific foundations of pharmacology, drug discovery and development, the attendant strategies and successful results. We also review and answer the major attacks on the philosophical and scientific foundations of modern pharmacology and drug therapy. Finally, we define the characteristics of an ideal drug. As an example of the principles and strategies of modern pharmacological sciences and their successful application, we focus on the discovery and development of proton pump inhibitors (PPIs) of stomach acid production. This class of drugs approaches the ideal and exemplifies successful application of modern pharmacological principles to drug discovery and development. Moreover, the use of PPIs as a pharmacological tool allowed the resolution of important scientific questions, e.g., the role of stomach acid in peptic diseases of the stomach, duodenum and esophagus.
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PMID:The power of pharmacological sciences: the example of proton pump inhibitors. 1644 24

H. pylori infection is a major pathogen inducing gastric mucosal inflammation and causing dysregulation of normal acid inhibitory regulatory mechanisms. The overall effect on gastric acid secretion is dependent on the location and severity of inflammation. Eradication results in healing of gastric mucosal inflammation, healing of peptic ulcers, prevention of new peptic ulcers, prevention or reduction in gastric cancer risk and in transmission of the infection. Neither H. pylori infection nor H. pylori eradication causes gastroesophageal reflux disease (GERD). H. pylori eradication also does not impede anti-secretory drug therapy of GERD. Misunderstandings of the negative association between H. pylori infection and GERD and/or Barrett's esophagus and misuse of the epidemiologic concept of ''protection'' led to considerable confusion and likely resulted in some patients receiving poor care. Current evidence is consistent with the notion that H. pylori should be eliminated whenever the organism is found. However, H. pylori infection has become increasing difficult to cure in part due to the emergence of antimicrobial resistance. In Western countries, triple therapy consisting of a proton pump inhibitor, amoxicillin and clarithromycin no longer achieves adequate eradication rates and will soon need to be abandoned. When used, legacy triple therapy should be given for 14 days. Fluorquinolones may temporarily be useful: 10-14 day duration is superior to 7 days. However, worldwide resistance is rapidly increasing. Other potential replacement therapies and strategies are discussed including sequential therapies, high-dose proton pump inhibitor plus amoxicillin, and new quadruple therapies.
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PMID:Current understandings of Helicobacter pylori, peptic ulcer and gastroesophageal reflux disease. 1697 68

During the last decade, clinical practice saw a rapid increase of patients with esophageal eosinophilia who were thought to have gastroesophageal reflux disease (GERD) but who did not respond to medical and/or surgical GERD management. Subsequent studies demonstrated that these patients had a "new" disease termed eosinophilic esophagitis (EE). As recognition of EE grew, so did confusion surrounding diagnostic criteria and treatment. To address these issues, a multidisciplinary task force of 31 physicians assembled with the goal of determining diagnostic criteria and making recommendations for evaluation and treatment of children and adults with suspected EE. Consensus recommendations were based upon a systematic review of the literature and expert opinion. EE is a clinicopathological disease characterized by (1) Symptoms including but not restricted to food impaction and dysphagia in adults, and feeding intolerance and GERD symptoms in children; (2) > or = 15 eosinophils/HPF; (3) Exclusion of other disorders associated with similar clinical, histological, or endoscopic features, especially GERD. (Use of high dose proton pump inhibitor treatment or normal pH monitoring). Appropriate treatments include dietary approaches based upon eliminating exposure to food allergens, or topical corticosteroids. Since EE is a relatively new disease, the intent of this report is to provide current recommendations for care of affected patients and defining gaps in knowledge for future research studies.
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PMID:Eosinophilic esophagitis in children and adults: a systematic review and consensus recommendations for diagnosis and treatment. 1791 4


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